Biography:

One of their most recent publications is Enhanced apoB48 metabolism in lipoprotein lipase X447 homozygotes. Which was published in journal Atherosclerosis.

More information about Melchior C. Nierman research including statistics on their citations can be found on their Copernicus Academic profile page.

Melchior C. Nierman's Articles: (2)

Enhanced apoB48 metabolism in lipoprotein lipase X447 homozygotes

AbstractRationaleLipoprotein lipase (LPL) X447 homozygotes are characterized by enhanced conversion of TRL apoB100. Here, we set out to investigate whether this LPL variant is also associated with enhanced apoB48 clearance. Therefore, we evaluated apoB48 kinetics in X447 homozygotes in the fed state by infusion of isotope l-[1-13C]-valine and subsequent compartmental modeling.Methods and resultsApoB48 metabolism was assessed in five X447 homozygotes (X/X genotype) and five S447 homozygotes (S/S genotype). Subjects were continuously fed and received infusion of stable isotope l-[1-13C]-valine. Results were analyzed by SAAM II modeling. Fasting (2.4-fold, p = 0.02) as well as non-fasting (1.6-fold, p = 0.09) apoB48 concentration was increased in the X447 homozygotes compared to S447 homozygotes. In addition, the X447 homozygotes exhibited a 1.7-fold higher apoB48 poolsize (p = 0.04). Interestingly, apoB48 fractional catabolic rate (FCR) was 1.9-fold higher (p = 0.007) and apoB48 synthesis was more than two-fold higher (p = 0.006) in the X447 homozygotes compared to S447 homozygotes.ConclusionIn the present study, we show that X447 homozygotes exhibit enhanced apoB48 clearance. Previously, these homozygotes were shown to present with enhanced apoB100 TRL conversion. Combined, this LPLS447X gain of function variant affects apoB48 as well as apoB100 TRL metabolism.

Carriers of the frequent lipoprotein lipase S447X variant exhibit enhanced postprandial apoprotein B-48 clearance

AbstractThe frequent lipoprotein lipase S447X variant (LPLS447X) is firmly associated with a lower incidence of cardiovascular disease, the mechanisms for which remain to be established. To further unravel these beneficial effects, we studied the consequences of LPLS447X heterozygosity on LPL mass and activity, as well as on the postprandial lipoprotein profile. Fifteen male heterozygous LPLS447X carriers and 15 matched control subjects received an oral fat load (30 g/m2). Lipid parameters were evaluated at baseline and 2, 3, 4, and 6 hours after fat loading. LPL concentration and activity were analyzed, and endothelial function was evaluated noninvasively as flow-mediated dilation of the brachial artery. Although baseline apoprotein B-48 (apoB48) levels were similar, the rise in apoB48 was attenuated in LPLS447X carriers with 25% lower peak values compared with controls (P = .04). In conjunction, LPLS447X carriers were characterized by a 2.4-fold increase in preheparin LPL mass (P < .0001). The decrease in postprandial flow-mediated dilation was comparable in both groups. LPLS447X carriers exhibit enhanced apoB48 clearance with concomitant increase in preheparin LPL mass, without changes in LPL activity. This combination might suggest a role for increased ligand action of LPL in LPLS447X carriers contributing to the cardiovascular protection in carriers of this mutation.

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